CA1147345A - Intermediate in the preparation of cyclopropylcarboxylate esters and process for its manufacture - Google Patents

Abstract

ABSTRACT
"NOVEL INTERMEDIATE IN THE PREPARATION OF CYCLOPROPYLCARBOXYLATE
ESTERS AND PROCESS FOR ITS MANUFACTURE"
3-Acetoxymethyl-2,2-dimethylcyclopropanecarbaldehyde di-methyl acetal, especially in the same stereoisomeric form as that of the cyclopropane ring in (+)-3-carene, is a novel intermediate useful in the manufacture of pyrethroid insecticides. It may be manufactured by a process characterised in that 2-(3-acetoxy-methyl-2,2-dimethylcyclopropyl)vinyl acetate is subjected to ozonolyis and the ozonolysis product so formed is subjected to reduction in the presence of methanol and an acetalizing cata-lyst.

Description

7~

"NOVEL INl~RMEDIATE IN THE PREPARATIO~ OF CYCLOPROPYLCARBOXYLATE
~- ESTERS AND PROCESS FOR ITS MANUFACTURE"

The invention relates to a compound which is a useful intermediate in the preparation Or cyclopropylcarboxylate esters.
The invention also relates to a process for the preparation of the compound.
The cyclopropylcarboxylate esters are insecticidally-aotive compounds known as ~pyrethroids" and as they combine exception-ally good insecticidal properties with a very low mammalian toxicity, they are of considerable interest to the agrochemical industry and much effort has been expended in finding conomic routes to them and~to their principal inSermediates.
The general formula of one class of these pyrethroid com-pound3 may be represented as Pollows:

1~ CH ~ ~ ~C003 where each asterisk denotes an asymmetric carbon atom; each X is a halogen atom; and R is a member Or a group of radicals known to impart insecticidal activity to the molecule, e.g. 3-phenoxy-benzyl or alpha-cyano-3-phenoxybenzyl. It is known that the stereoisomeric form of the acid portion of the ester Or formula I
should be ir. the (1R, cis) form for maximum insecticidal activity i.e. the absolute configuration at carbon atom 1 i~ R and the ,-two hydrogen atoms on carbon atoms 1 and 3 are in a CiS relationship. This nomenclature is known as the Elliott nomenclature and is defined in M. Elliott, A.W. Farnham, N.F. James, P.H. Needham and D.A. Pullman, Nature, 1974, 248, 710.
It follows, therefore, that if these stereoisomeric esters of formula I are to be prepared, either a stereospecific chemical route is required or the desired stereo-isomer must be obtained from a racemic form by physical separation techniques. The latter are expensive and laborious and not readily employed on an industrial scale. The Applicant has found a stereospecific route which uses as starting material the naturally-occurring substance (+)-3-carene whose formula is as follows:

h (II) CH3 ~

CH3 `H

This compound is an inexpensive readily-available natural terpene and in our copending Canadian patent application 316,588 is disclosed a route to the ~lR, cis)-acid portion of the pyrethroid ester of formula I starting from (+)-3-carene and proceeding via the novel cyclopropane compound according to the invention.
The present invention provides 3-acetoxymethyl-2~2-dimethylcyclo-propanecarbaldehyde dimethyl acetal whose formula is:-H \ CH2-O-CO-CH3 CH3~ / 3 ~III) / \ O-CH3 ' ~ `

- 2 -

3~4~3At5 Preferably the compound of formula III is in the same stereoisomeric form as that of the cyclopropane ring of (+)-3-carene because this form leads to com-pounds of general formula I ~R=H) in the ~lR, cis) form; such compounds gen-erate optimum levels of insecticidal activity in the pyrethroid end-product.
The compound III or its preferred stereoisomeric form may be pre-pared by methods know per se, for example from derivatives of (~)-3-carene employing ozonolysis and subsequent reduction of the peroxidic ozonolysis products formed, see for example, Chemical Reviews 58 ~1958) 925-995. It has been found that the compound may be conveniently prepared by a method which is characterised in that 2-~3-acetoxymethyl-2,2-dimethylcyclopropyl)vinyl acetate of formula:-H ~ CH2-0-CO-CH

CH3 ~ CH=CI~-O-CO-CH3 (IV) is subjected to ozonolysis and the ozonolysis product so formed is subjected to reduction in the presence of methanol and an acetalizing catalyst. Preferably Compound IV is employed in the same stereoisomeric form as that of the cyclo-propane ring of ~)-3-carene.
The ozonolysis is preferably carried out in the presence of methanol.
The reduction of the ozonlysis product formed is suitably carried out with dimethyl sulphide. p-Toluenesulphonic acid is a good acetalizing catalyst.
As has been indicated above a multi-stage process for the preparation of insecticidally active compounds, starting with ~)-3-carene and in which the compound according to the invention is employed as intermediate, is described inCanadian patent application 316,588.
The following Example further illustrates the invention. Yields and "~ - 3 -- ~,47345 purities were determined by means of gas-liquid chromatography and nuclear magnetic resonance (MMR) spectroscopy. The NMR data quoted were recorded at 90 MHz using solutions of the compounds in deuterochloroform.
Example - Preparation of a stereoisomer of 3-acetoxymethyl-2,2-dimethylcyclo-propanecarbaldehyde dimethyl acetal (Compound III) derived from (+)-3-carene.

.. _ . _ _ ... ... _ r~

3~

(a) Preparation o~ a stereoisomer of 1~(2-dimethoxyethyl)-2,2-. . _ .
dimethyl-3-(2-oxo-propyl)cyclopropane (compound A) A Plask was charged with (~)-3-carene (375 mmol) and water-free methanol (150 ml) and kept at a temperature of _60C. Then, a mixture of ozone and oxygen was passed through the liquid in the flask at a rate of 70 l/h (corresponding to 75 mmol of ozone per hour) until the ~+)~-3-carene was fully converted t5 hours).
The reactioh mixture formed was allowed to adopt a temperature of 20-C, dimethyl sulphide (750 mmol) and p-toluenesulphonic acid (1.74 mmol) were added and the mixture formed was stirred for four days at 20 C. At the end of this period the (+)-3-carene was fully converted into compound A~ Methanol and dimethyl sulphide were evaporated from the reaction mixture, at a pressure of 24 mbar (40C), diethyl ether (150 ml) was added to the residu obtained, the solution formed was washed with a 5 %w aqueous solution of sodium hydrogen carbonate (30 ml), with four 30 ml portion of water, the washed solution was dried over anhydrous magnesium sulphate and the solvent was evaporated from the dried liquid at a temperature of 30 C and a pressure of 24 mbar to give a residue (68.9 g). This residue was distilled at 83 C/l mbar to give a fraction consisting of the cis isomer of yield 73.5~.
(b) Preparation oP a stereoisomer of 2-(2,2-dimethoxyethyl)-3,3-dimethylcyclopropylmethyl acetate (compound B) .. . . . . ~
The contents of a flask chargèd with compound A (200 mmol) prepared a~ in (a) in this Example, chIoroform (300 ml) and 3-chloroperbenzoic acid (384 mmol) were stirred at 20C ~or 24 hours. The precipitate formed was separated by filtration, the - filtered precipitate was mixed with n-pentane (150 ml), the mixture was separated by filtration, the combined filtrates were washed with two 50 ml portions oP a 5~ solution of sodium car-bonate in water and with two 50 ml portions of water, the washed liquid was dried over anhydrous magnesium sulphate and the solvent was evaporated from the dried li9uid at a temperature of 90 C and a pressure of 20 mbar to give a residue containing compound B in a yield of 97~. The content of compound B in the :

~73'~5 resldue was 92~; only the cis isomer had been formed.
tc) Preparation of a stereoisomer of 2,2_dimethyl-3-(2-formyl-_thyl)-cyolopropylmethyl acetate (oompound C) The oontents of a flask charged with compound B (218 mmol in the re~idue prepared as desoribed in b), acatic acid (40 ml) and : water ~20 ml) were stirred at 60C during 2.5 hours. The solvent was evaporated from the reaction mixture at a temperature of 45 C and a pressure of 2~ mbar, the residue obtained was taken up in diethyl ether (150 ml), the solution obtained was washed with two 50 ml portions of a 5 %w solution o~ sodium hydrogen carbonate in water and with two 50 ml portions of water, the washed solution was dried over anhydrous magnesium sulphate and the solvent was evaporated from the dried liquid at a temperature of 30 C and a pressure of 24 mbar to give a residue containing compound C in a yield of 80~; the content of compound C in the residue was 85%. Only the cis isomer had been formed.
(d) Preparation of a stereoisomer of 2_(3_acetoxymethyl_2,2_ dimethylcyclopropyl)vinyl acetate (compound D) The contents of a flask charged with compound C (175 mmol in the residue prepared as described in C), triethylamine (386 mmol) and acetic anhydride (350 ml) were stirred at 20C for 18 hours.
The solvent was evaporated from the reaction mixture at a temper-ature of 50 C and a pressure of 20 mbar, the residue obtained was taken up in diethyl ether (150 ml), the solution obtained was washed with five 40ml portions of water, the washed solution was dried over anhydrous magnesium sulphate and the solvent was evaporated from the dried liquid at a temperature of 40C and a pressure of 20 mbar to give a residue containing compound D in quantitative yield. The content of compound D in the residue was 88.4p, The orientation to the cyclopropane ring was still cis.

~1~734~;

(e) Preparation Or a stereoisomer Or compound III.
A f`lask was charged with compound D t175 mmol, present in the residue obtained in d), water-free methanol (200 ml) and p-toluenesulphonic acid (1.16 mmol) and kept at a temperature of _65C. Then, a mixture of o~one and oxygen was passed through the liquid in the Plask at a rate Or 60 l~h (corresponding to 70 mmol of ozone per hour) until compound D was fully converted (2.5 hours). The reaction mixture formad was allowed to adopt a temperature Or 20C, dimethyl sulphide (350 mmol) was added and the mixture formed was stirred for 17 hours at 20C. Methanol and dimethyl sulphide were evaporated from the reaction mixture, at a pressure Or 16 mbar, diethyl ether (50 ml) was added to the residue obtained and so much Or a saturatad aqueous solution Or sodium bicarbonate was added to the mixture that the pH reached a ~alue Or 7. Then, the mixture was washed with three 50-ml por-tions of water, the washed liquid was dried over anhydrous magnesium sulphate and the solvent was evaporated from the dried liquid at a temperature Or 40 C and a pressure of 24 mbar to give a residue (29.6 g) containing compound III (yield 78%). Only the cis isomer had been formed.
The NMR spectrum o~ compound III showed the following absorp-tions:
= 3.38 ppm (singlet, C-O-CH3)~ ~ = 1.18 ppm (singlet, H3C-C-CH3) ~ - 4.2 ppm (multiplet, H-C-O-CH3)~ - 1.1 ppm (multiplet, H-C-C-CH2) ~ = 1.2 ppm (multiplet, H-C-C-(H)-~ = ~.2 ppm (multiplet, H-C-CH ) -(aCH3)2) ~ 2 = 1.18 ppm(singlet, H3C-C-CH3) ~ = 2.1 ppm (singlet, H3C C(O)-O-) The stereoisomer of compound III was converted into a tereoisomer Or 3-(2~2-dichlorovinyl)-2,2-dimethyl cyclopropylcarboxylic acid (Formula I: R . H : X = Cl) and it was found that it3 stereoisomeric form was the same as the (1R, cis) form of the acid, the known activ2 acid portion Or certain pyrethroid esters.

Claims (7)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. 3-Acetoxymethyl-2,2-dimethylcyclopropanecarbaldehyde di-methyl acetal.

2. Compound according to claim 1 characterised in that it is in the same stereoisomeric form as that of the cyclopropane ring of (+)-3-carene.

3. A process for preparing the compound claimed in claim 1 characterised in that 2-(3-acetoxymethyl-2,2-dimethylcyclopropyl) vinyl acetate is subjected to ozonolysis and the ozonolysis pro-duct so formed is subjected to reduction in the presence of methanol and an acetalizing catalyst.

4. A process according to claim 3 characterised in that 2-(3-acetoxymethyl-2,2-dimethylcyclopropyl)vinyl acetate is employed in the same stereoisomeric form as that of the cyclopropane ring of (+)-3-carene.

5. A process according to claim 4 characterised in that the ozonolysis is carried out in the presence of methanol.

6. A process according to any one of claims 3, 4 or 5 characterised in that the reduction is effected with dimethyl sul-phide.

7. A process according to claims 3, 4 or 5 characterised in that the acetalizing agent is p-toluenesulphonic acid.